Differentiation of Glioblastomas from Metastatic Brain Tumors by Tryptophan Uptake and Kinetic Analysis: A Positron Emission Tomographic Study with Magnetic Resonance Imaging Comparison

Abstract

Differentiating high-grade gliomas from solitary brain metastases is often difficult by conventional MRI; molecular imaging may facilitate such discrimination. We tested the accuracy of alpha[11C]methyl-L-tryptophan (AMT)-PET imaging to differentiate newly-diagnosed glioblastomas from brain metastases. AMT-PET was performed in 36 adults with suspected brain malignancy. Tumoral AMT accumulation was measured by standardized uptake values (SUVs). Tracer kinetic analysis was also performed to separate tumoral net tryptophan transport (by AMT volume of distribution, VD′) from unidirectional uptake rates using dynamic PET and blood input function. Differentiating accuracy of these PET variables was evaluated and compared to conventional MRI. For glioblastoma/metastasis differentiation, tumoral AMT SUV showed the highest accuracy (74%) and the tumor/cortex VD′ ratio had the highest positive predictive value (82%). The combined accuracy of MRI (size of contrast enhancing lesion) and AMT-PET reached up to 93%. For ring-enhancing lesions, tumor/cortex SUV ratios were higher in glioblastomas than in metastatic tumors and could differentiate these two tumor types with >90% accuracy. These results demonstrate that evaluation of tryptophan accumulation by PET can enhance pre-treatment differentiation of glioblastomas and metastatic brain tumors. This approach may be particularly useful in patients with a newly-diagnosed solitary ring-enhancing mass.

Assessment of Tryptophan Uptake and Kinetics Using 1-(2-18F-Fluoroethyl)-l-Tryptophan and α-11C-Methyl-l-Tryptophan PET Imaging in Mice Implanted with Patient-Derived Brain Tumor Xenografts

“…Nevertheless, the high 18 F-FETrp uptake in the bladder and pancreas suggests that this tracer would not allow visualization of tumors in these organs because of high background activity. Despite the differences in distribution, both tracers demonstrated similarly low and continuous brain accumulation, suggesting that 18 F-FETrp will be suitable for the imaging of intracranial brain tumors as previously established with 11 C-AMT (18)(19)(20)(21)(22)(23)(24)(25)(26).…”

“…Our previous PET studies demonstrated differential 11 C-AMT transport and trapping in human gliomas, lung cancer, and breast cancer, tumors that expressed both the L-type amino acid transporter 1 and IDO1 (23,26,(45)(46)(47). However, the widespread use of 11 C-AMT for cancer imaging is not feasible because of its short half-life and tedious radiosynthesis.…”

“…These studies demonstrated variably high 11 C-AMT uptake in gliomas (18,23,24) and meningiomas (21) and showed strong prognostic value for survival in patients with recurrent glioblastoma (20). Furthermore, 11 C-AMT uptake characteristics distinguished recurrent gliomas from radiation injury (25) and glioblastoma from metastatic brain tumors (26), allowing tryptophan PET imaging as a possible clinical diagnostic tool. The development of a tryptophan analog with a longer half-life isotope such as 18 F would permit widespread clinical application of tryptophan PET imaging.…”

Brain metastases: neuroimaging

“…For instance, Kamson and colleagues (2013) used a relatively new PET tracer that is a tryptophan analogue (11C-alphamethyl- l -tryptophan), and compared enhancing lesions that were either glioblastoma ( n = 19) or metastases ( n = 31). Based on this method they were able to differentiate glioblastoma from metastases (glioblastoma had higher uptake) with 74% accuracy.…”

Multiple ring enhancing lesions in a patient with unilateral limb jerking

“…In one study of ring enhancing Brought to you by | MIT Libraries Authenticated Download Date | 5/10/18 12:13 AM lesions, Kamson and colleagues reported that the ratio of tumor to cortex standard uptake value (SUV) was significantly higher in GBM than in metastatic tumors. The SUV value alone could distinguish the two causes for RELs with an accurancy of greater than 90% [5].…”